TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus

PLoS Pathogens

Ruth E. Watkinson¹  William A. McEwan¹  Jerry C. H. Tam¹  Marina Vaysburd¹  Leo C. James¹ 

[1] Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom

关键词: Antibodies;    Virions;    Viral genomics;    Adenoviruses;    Small interfering RNAs;    Rhinovirus infection;    Viral genome;    Mammalian genomics;   

DOI  :  10.1371/journal.ppat.1005253

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Encapsidation is a strategy almost universally employed by viruses to protect their genomes from degradation and from innate immune sensors. We show that TRIM21, which targets antibody-opsonized virions for proteasomal destruction, circumvents this protection, enabling the rapid detection and degradation of viral genomes before their replication. TRIM21 triggers an initial wave of cytokine transcription that is antibody, rather than pathogen, driven. This early response is augmented by a second transcriptional program, determined by the nature of the infecting virus. In this second response, TRIM21-induced exposure of the viral genome promotes sensing of DNA and RNA viruses by cGAS and RIG-I. This mechanism allows early detection of an infection event and drives an inflammatory response in mice within hours of viral challenge.

【 授权许可】

CC BY